Antibody conjugation to cytotoxic drugs is one of the most promising ways to enhance the therapeutic activity of antibodies and reduce the systemic toxicity of drugs. At least six antibody drug conjugates (ADCs) have progressed into clinical development. One feature of antibodies that potentially limits the therapeutic index (i.e., maximum tolerated dose/minimum curative dose) of an ADC is non-target toxicity. Such specificity may be specific or non-specific. Non-target uptake of ADCs may lead to ADC catabolism, drug release and/or toxicity.
Accordingly, there is a need for ADCs and other target binding agents that can exert a clinically useful cytotoxic, cytostatic, or immunomodulatory effect on target cells, particularly without exerting undesirable effects on non-target cells. Such ADCs and other target binding agents would be useful therapeutic agents against cancers that express a target antigen or immune disorders that are express target antigens. The present invention satisfies this and other needs. (The recitation of any reference in this application is not an admission that the reference is prior art to this application).